Complete repopulation of mouse mitochondrial DNA-less cells with rat mitochondrial DNA restores mitochondrial translation but not mitochondrial respiratory function

By the fusion of mtDNA-less (rho(0)) cells of Mus musculus domesticus with platelets from different species, mtDNA repopulated cybrids were obtained f or finding the mtDNA species that could induce mitochondrial abnormalities. Expression of mitochondrial dysfunction might be expected in these cybrids due to incompatibilily between nuclear and mitochondrial genomes from diff erent species. The results showed that mouse rho(0) cells could receive mtD NA from a different mouse species, M. spretus, or even mtDNA from thee rat, Rattus norvegicus, and that the introduced rat mtDNA, but not M. spretus m tDNA, caused mitochondrial dysfunction, even though rat mtDNA could restore normal mitochondrial translation in the cybrids. Considering that mitochon drial respiratory complexes consist of nuclear DNA- and mtDNA-coded polypep tides, these observations suggest that the nuclear and mitochondrial intera ctions required for replication, transcription, and translation of introduc ed rat mtDNA must be less stringently controlled than those required for fo rmation of normal respiratory complexes. As no procedure for introduction o f mutagenized mouse mtDNA into living cells has yet been established, these findings provide important insights into generating mtDNA-knockout mice.